Exploration of Immune-Related Transcription Control/Regulation in Intracranial Aneurysm Through KEGG Analysis and in-vivo Validation.

Abstract

Background: Intracranial aneurysms (IAs), a leading cause of subarachnoid hemorrhage, rank second only to cerebral thrombosis and hypertensive intracerebral hemorrhage among cerebrovascular diseases. However, the understanding of the regulatory mechanisms associated with IAs remains limited currently.

Methods: We obtained the GSE122897 dataset and analyzed differential expression genes (DEGs) from control, Ruptured intracranial aneurysm (RIA) and Unruptured intracranial aneurysm (UIA) samples under varied conditions. The correlation and differences of immune cell types across groups were examined. TF-target genes were obtained from the hTFtarget database, five immune-related TFs were identified and their expression was normalized and validated in an IA mouse model via qRT-PCR and Western blot analysis.

Results: 1852 up-regulated and 971 down-regulated DEGs in Control vs RIA, 583 up-regulated and 389 down-regulated genes in Control vs UIA groups. Most DEGs enriched in immune response, such as circulating immunoglobulin, immunoglobulin mediated immune response and B cell mediated immunity. A TF-target regulatory network of these DEGs were predicted and suggested that TF RUNX3 has the most target genes, including SBDS, ARTN, LTA, GMFB and so on. qRT-PCR and Western blot validated the higher expression of DBP, NR3C2 and ZNF711, and lower expression of RUNX3 and ZFN711 in IA mice.

Conclusion: 5 key TFs DBP, RUNX3, SPIB, NR3C2 and ZNF711 were found to be related to immune response and their up/down-regulated expression were observed in IA mice. As RUNX3, SPIB and NR3C2 shared common target genes, they may involved in co-regulated pathway during IA progression.